Synonym name: Bilobalide A
Catalogue No.: BP0274
Cas No.: 33570-04-6
Formula: C₁₅H₁₈O₈
Mol Weight: 326.301
Botanical Source: leaves of Ginkgo biloba (ginkgo)

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.

Inquire for bulk scale.

References

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Bilobalide A (CAS No.: 33570-04-6) is one of the important sesquiterpene trilactone natural products found in ginkgo leaves, attracting significant attention for its unique chemical structure and significant neuroprotective activity. As a key ingredient in traditional Chinese medicine and modern health supplements, ginkgo leaf extract is widely used as an adjunct treatment for neurological diseases. Ginkgo lactones, as one of the active components in ginkgo biloba leaves, have demonstrated neuronal protective and nourishing effects, especially showing good therapeutic potential in neurodegenerative disease models such as cerebral ischemia-reperfusion injury. In recent years, with advances in molecular biology and pharmacological technologies, the mechanism of action of ginkgo lactone has gradually been revealed, involving multiple cellular signaling pathways and key molecular targets. This paper aims to systematically review the chemical structure, pharmacological activity, mechanism of action, druggability, and clinical application prospects of ginkgo lactone, providing a theoretical foundation and reference for subsequent research and development.

Chemical structure and physicochemical properties

Ginkgo lactone belongs to the sesquiterpene trilactone class of compounds, with a molecular formula of C15H18O7 and a molecular weight of 310.30. Its structural feature is a tricyclic lactone backbone, containing multiple hydroxyl and lactone rings, giving it high polarity and abundant hydrogen bond acceptors (8). The topological surface area (TPSA) of ginkgo lactone is 142.12 Ų, indicating strong polarity and good water solubility. The LogP value was -0.97, indicating strong hydrophilicity, which is beneficial for distribution and dissolution within organisms. This compound has high blood-brain barrier penetration (BBB permeability), which is especially important for neurological drugs. The combined physicochemical properties enable ginkgo lactone to effectively target central nervous system targets in the body and exert its pharmacological effects.

Plant Origins and Extraction Methods

Ginkgo lactones are mainly found in ginkgo leaves (Ginkgo biloba L.). As an ancient gymnosperm, ginkgo's leaves are rich in various bioactive components, including flavonoids, terpene lactones, and organic acids. Ginkgo lactone is one of the representative components of sesquiterpene lactone in ginkgo leaf. Although its content is not as abundant as flavonoids, its biological activity is outstanding.

The extraction method mainly relies on organic solvent extraction and chromatographic separation technology. Common extraction solvents include ethanol, methanol, and their aqueous solutions. Using ultrasound-assisted extraction or reflux extraction can improve extraction efficiency. Subsequently, separation and purification were carried out using silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other methods. In recent years, supercritical fluid extraction and membrane separation technologies have also been applied to the extraction and purification of ginkgo lactone, significantly improving yield and purity. Purified ginkgo lactones can be identified and quality controlled using technologies such as mass spectrometry and nuclear magnetic resonance (NMR).

Pharmacological activity research

The pharmacological activity of ginkgo lactone mainly focuses on neuroprotective and anti-apoptotic effects. Its most notable biological function is inhibiting the mediated choline efflux mediated by NMDA (N-methyl-D-aspartic acid) receptors, with an IC50 of about 2.3 μM, indicating its potential role in regulating neurotransmitter release and neuroexcitability. NMDA receptor overactivation is the pathological basis for cerebral ischemia-reperfusion injury and various neurodegenerative diseases. Ginkgo lactone protects neurons by inhibiting this pathway.

Additionally, ginkgo lactone can activate the PI3K/Akt signaling pathway within nerve cells, promoting cell survival and inhibiting apoptosis. In vitro studies have shown that in the human neuroblastoma cell line SH-SY5Y, ginkgo lactone significantly reduces cell apoptosis rate and enhances cell viability. Its antioxidant activity has also been confirmed, reducing neuronal damage caused by oxidative stress by regulating the expression of superoxide dismutase (SOD1, SOD2) and nitric oxide synthase (NOS3).

In cerebral ischemia-reperfusion injury models, ginkgo lactone can regulate various key molecules, such as anti-apoptotic protein BCL2, pro-apoptosis protein BAX, apoptosis-executing enzyme CASP3, inflammatory transcription factor NFKB1, and angiogenesis factor VEGFA, collectively exerting neuroprotective effects. Its multi-target and multi-mechanism pharmacological properties have made it a research hotspot in the field of neuroprotection.

Mechanism of action and molecular targets

The neuroprotective mechanisms of ginkgo lactone involve multiple molecular targets and signaling pathways, mainly including:

1. NMDA receptor regulation
   Ginkgo lactone can inhibit NMDA receptor-mediated hyperexcitation, reduce glutamate-induced neurotoxicity, lower choline efflux, and alleviate neuronal damage caused by excitotoxicity. GRIN1, as a subunit of the NMDA receptor, is its key target.

2. PI3K/Akt signaling pathway activated
   By activating the PI3K/Akt pathway, ginkgo lactone promotes cell survival signaling, inhibits the expression of apoptosis-related proteins, reduces CASP3 activation, and maintains normal cell function and structural integrity.

3. Regulates apoptosis-related proteins
   Ginkgo lactone upregulates the anti-apoptotic protein BCL2 and downregulates the pro-apoptosis protein BAX, balancing intracellular apoptosis signals and reducing apoptosis.

4. Antioxidant and anti-inflammatory effects
   By regulating the expression of antioxidant enzymes such as SOD1 and SOD2, ginkgo lactone reduces oxidative stress damage. At the same time, it inhibits NFKB1-mediated inflammatory responses and reduces neuroinflammation levels.

5. Promotes angiogenesis and repair
   Ginkgo lactone can regulate VEGFA expression, promote angiogenesis in ischemic areas, improve local blood supply, and promote neurological recovery.

6. Regulates nitric oxide synthase
   By regulating NOS3 activity, ginkgo lactone participates in vasodilation and neuroprotection, maintaining cerebral hemodynamic stability.

In summary, ginkgo lactone regulates neuronal excitability, oxidative stress, apoptosis, and inflammatory responses through multi-target synergy, forming a complex neuroprotective network.

Druggability evaluation and pharmacokinetics

Ginkgo lactone exhibits good druggability. Its molecular weight is moderate (310.3 Da), meeting the basic requirements of the Lipinski rule. The LogP value was -0.97, indicating strong hydrophilicity, which is beneficial for distribution and bioavailability. High TPSA (142.12 Ų) reflects its high polarity, yet it can still effectively cross the blood-brain barrier to meet the needs of central nervous system drugs.

Toxicological evaluation showed that ginkgo lactone is non-hepatotoxic or cardiotoxic, and does not inhibit hERG channels, reducing the risk of drug-induced arrhythmias. The Ames test result was negative, indicating it is not genotoxic and has a relatively high safety profile.

Pharmacokinetics, although systematic research on ginkgo lactone is currently limited, studies have shown that it is well absorbed orally and can effectively enter brain tissue. Its metabolic pathway mainly involves liver enzyme systems, and the metabolites require further identification. In the future, systematic pharmacokinetic and toxicological studies are needed to clarify its in vivo behavior and safe dosage range.

Prospects and outlooks for clinical applications

Based on the neuroprotective effects and good druggability of ginkgolactone, its application prospects are broad in cerebral ischemia-reperfusion injury, neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease), and other neurological disorders. Ginkgo lactone offers new ideas for comprehensive treatment of neurological diseases through multi-target and multi-mechanism actions.

Currently, ginkgo leaf extract has been widely used in clinical adjuvant therapy. Ginkgo lactone, as one of its active ingredients, is expected to be developed into a single-component neuroprotective drug in the future. By combining modern drug delivery technologies, such as nanocarriers and brain-targeted delivery systems, its efficacy and safety are expected to be further enhanced.

In addition, the potential of ginkgo lactone for antioxidant, anti-inflammatory, and neural repair also opens up its application in chronic neurological diseases and brain injury rehabilitation. Future research should focus on clinical pharmacology, dose optimization, and long-term safety evaluation to promote clinical translation.

Conclusion

Ginkgo lactone, an important squiterpene trilactone component in ginkgo biloba leaves, demonstrates excellent pharmacological activity and drug potential due to its unique chemical structure and multi-target neuroprotective effects. By inhibiting NMDA receptor-mediated neurotoxicity, activating the PI3K/Akt signaling pathway, and regulating apoptosis and antioxidant mechanisms, it effectively prevents neuronal damage and apoptosis, showing particularly significant protective effects in cerebral ischemia-reperfusion injury.

Druggability evaluations have shown that ginkgo lactone has good safety and blood-brain barrier penetration ability, laying the foundation for its development as a central nervous system drug. In the future, combined with modern drug development technologies, ginkgo lactone is expected to become a novel drug for treating neurological diseases, providing effective clinical treatment options.

In summary, ginkgo lactone, as an important research subject in the field of natural product pharmacology, has broad prospects for research and application, and is worthy of in-depth exploration and development.